Phosphorylation and dephosphorylation of the enzymes controlling rate-limiting metabolic steps is one of the most important mechanisms by which cellular metabolism is controlled by hormones and other regulators. Glycogen synthase and phosphorylase kinase are regulated by this mechanism in response to hormonal actions. These enzymes can be phosphorylated and dephosphorylated, respectively, by multiple forms of protein kinases and phosphatases. It is not entirely understood how hormones affect the various protein kinases and phosphatases which in turn influence the activities of glycogen synthase and phosphorylase kinase. The purposes of this project are: (1) to define the regulation of glycogen synthase and phosphorylase kinase activities by protein kinases and phosphatases; (2) to determine the defects in glycogen metabolism resulting from streptozotocin-induced diabetes in rats; (3) to elucidate the hormonal regulations of glycogen metabolizing enzymes in rat hepatocytes grown in culture; and (4) to use glycogen synthase and phosphorylase kinase as model systems to unfold the regulatory mechanisms for multiple protein kinases and phosphatases in response to hormonal actions.